Open AccessA comprehensive targeted next‐generation sequencing panel for genetic diagnosis of patients with suspected inherited thrombocytopenia
Author(s) -
Johnson Ben,
Doak Rachel,
Allsup David,
Astwood Emma,
Evans Gillian,
Grimley Charlotte,
James Beki,
Myers Bethan,
Stokley Simone,
Thachil Jecko,
Wilde Jonathan,
Williams Mike,
Makris Mike,
Lowe Gillian C.,
Wallis Yvonne,
Daly Martina E.,
Morgan Neil V.
Publication year - 2018
Publication title -
research and practice in thrombosis and haemostasis
Language(s) - English
Resource type - Journals
ISSN - 2475-0379
DOI - 10.1002/rth2.12151
Subject(s) - exome sequencing , dna sequencing , gene , medicine , genetic testing , genetic diagnosis , genetics , biology , mutation
Background Inherited thrombocytopenias ( IT s) are a heterogeneous group of disorders characterized by low platelet counts and often disproportionate bleeding with over 30 genes currently implicated. Previously the UK ‐ GAPP study using whole exome sequencing ( WES ) identified a pathogenic variant in 19 of 47 (40%) patients of which 71% had variants in genes known to cause IT . Aims To employ a targeted next‐generation sequencing platform to improve efficiency of diagnostic testing and reduce overall costs. Methods We have developed an IT ‐specific gene panel as a pre‐screen for patients prior to WES using the Agilent SureSelect QXT transposon‐based enrichment system. Results Thirty‐one patients were analyzed using the panel‐based sequencing, of which; 10% (3/31) were identified with a classified pathogenic variant, 16% (5/31) were identified with a likely pathogenic variant, 51% (16/31) were identified with variants of unknown significance, and 23% (7/31) were identified with either no variant or a benign variant. Discussion and Conclusion Although requiring further clarification of the impact of the genetic variations, the application of an IT ‐specific next generation sequencing panel is an viable method of pre‐screening patients for variants in known IT ‐causing genes prior to WES . With an added benefit of distinguishing IT from idiopathic thrombocytopenic purpura ( ITP ) and the potential to identify variants in genes known to have a predisposition to hematological malignancies, it could become a critical step in improving patient clinical management.